Aging leads to degenerative change in multiple systems and cell types. These losses induce the functional decline of specific physiological systems that contribute to progressive morbidity and ultimately to death. Two fundamental questions for basic gerontology arise from these central observations. What are the processes of intrinsic physiological decline in structure and function that lead to the eventual expression of specific geriatric disorders? To what extent are different phenotypes of functional aging coordinately regulated by common factors of an underlying aging process? This program project will address these questions with integrated research on functional aging of a genetic model system, Drosophila melanogaster. To achieve this goal, our program has four overall aims. 1) Establish multiple models of functional aging in Drosophila melanogaster with high physiological relevance to human senescent phenotypes, specifically in the senescence of cardiac, immune and sleep. 2) Assess how insulin/IGF and TOR regulation of lifespan affects independent and conglomerate axes of functional aging. 3) Discover pathogenic mechanisms underlying age dependent decline in cardiac, immune and sleep by methods of genetic manipulation including forward genetic screens and transgenic analysis of candidate factors. 4) Assess whether apparently divergent, asynchronous aspects of functional senescence are driven by a common process of aging. REVIEW OF INDIVIDUAL COMPONENTS OF THE PROGRAM PROJECT CORE A: ADMINISTRATIVE CORE, Dr. Rolf Bodmer, Core Leader (CL) DESCRIPTION (provided by applicant): Core A has the role to provide the leadership, interaction and coordination between the different projects of this PPG in order to facilitate them in meeting their scientific goals. Core A will oversee the organization of bi-annual meetings of the project leaders, organize annual meetings of the project leaders with the Scientific Advisory Board (SAB) and to review progress on the overall goals of the PPG as a whole. The PI of this PPG assisted by administrative personnel will assure seamless operation of the scientific agenda and administrative matters. Core A will also provide the administrative support, which includes the monitoring of funds and research allocations. The PI will review expenditures and resource allocations for the projects and cores, at least twice a year. The administrative core will also be responsible for collating the reports from the scientific advisory boards, as well as writing and transmitting the annual progress report to NIA. The PI of Core A will consult with a statistician from the nearby Department of Mathematics at the University of California at San Diego to provide statistical services. These services will be sought for consultation in biostatistical analysis of data from the various assays of the projects (for example, PCR, cardiac pacing, gut motility, sleep bout frequency, and many more). In addition, Core B leader Dr. Tatar and Dr. Gibson, a qualitative geneticist, will provide expert advice in biostatistics. Core A will oversee the launch and maintenance of a Web page for this PPG, which will allow distribution of findings among the global community, while enabling sharing protocols, reagents as well as information among the projects in real time.